key: cord-0041403-9h3ltqdi
authors: Hebden, S. P.
title: THE ANTHELMINTIC ACTIVITY OF THIABENDAZOLE (M.K.360)
date: 2008-03-10
journal: Aust Vet J
DOI: 10.1111/j.1751-0813.1961.tb03921.x
sha: 5b2085d712b40921fe657ec6eb5346b413a54983
doc_id: 41403
cord_uid: 9h3ltqdi

nan

The use of anthelmintics for worm control is an important part of sheep management in this country and in the evaluation of a new product certain fundamental requirements must be carefully borne in mind. First, it should be e&kient against both mature and immature parasites over a broad spectrum, secondly, it must be relatively non-toxic and thirdly, the cost to the user must be acceptable. In a study of the first two requirements phenothiazine may be used for the purpose of comparison.

For many years phenothiazine has held pride of place as the most efficient and the safest anthelmintic known for gastro-intestinal nematodes in sheep and although a number of other chemical products have been tried, with more or less success, none until recently has presented a serious challenge to its supremacy. This supremacy has been enhanced by the new formulations now available as the direct result of considerable scientific investigation that showed the important part played by particle size and purity of the phenothiazine. Gordon (1956) demonstrated the necessity for a fine particle size and Forsyth (1961) showed that a product of high purity is r q h d for maximum etlkhcy. Forsyth concluded that a RakrimmR purity of 85% is I~C~BEsary to obtain amsistestly Boofi anthelmintic results, ptulictdady in t&e control of Ostertagia and Tricho*mgylus speaks. In spite of the anthelmintic s u p i u d t y sbown by phenothiazine there is ample mom for improvement as regards its action on maay of the nematode parasites of sheep. Resistance by the worms has been demonstrated in the U S A . (Drudge cz d. (1957) (a, b) ) and is suspected to exist in Australia. A further cause for concern is the occasional reports of losses following its use received by the N.S.W. Department of Agriculture.

The advent of another anthelmintic with rep o d high efficiency over a broad spectrum and a high degec of safety tras created considerable intern, and samples of this chemical--60 -w e r e received by the N.S.W. Department It is a fine, colourless, insoluble powder, odourless and tasteless. It does not stain the wool or skin. The sample used was formulated by the above Laboratories as a suspension in water, some of the solids of which settled readily and were difficult to resuspend. The suspension was stated to contain 2.28 grams of the active principal in each fluid ounce, which is, therefore, sufficient for a sheep of 100 Ib. live weight at the dose rate of 50 mg/Kg. The phenothiazine used for comparative purposes was a commercially prepared powder con-taining 90% w/w technical phenothiazine shown by analysis to be 93% pure and having a particle surface area of 17,100 cm2/g. (by air permeability). Before administration, tap water was added to the powder to give a 50% suspension. From this flock 30 weaners were selected, weighed and ear tagged and these were divided at random into three groups of ten. Faecal samples were collected from all thirty, and five animals of Group 1 (untreated controls) were slaughtered for immediate examination.

At the same time, the ten sheep in Group 2 were dosed with MK 360 at 50 mk/Kg. through a rubber tube inserted into the oesophagus. The ten sheep in Group 3 were similarly drenched with phenothiazine at 600 mg/Kg. All the sheep ( 2 5 ) remaining in the trial were then turned into a paddock and held for 6 days prior to slaughter.

Examination of all faecal samples and the gastrointestinal organs from the five controls was carried out in the laboratory at Glenfield. Faecal egg counts were made using the methods outlined by Whitlock & Gordon (1939) . The abomasa, small and large intestines were examined separately, contents and mucosal scrapings of the first two being washed into a 60 mesh sieve and then diluted to two litres with water. All worms present in a 40 ml. aliquot were identified and counted. In the examination of the large intestines, a 40 mesh sieve was used and all worms present were counted.

Six days after treatment the 25 remaining sheep were killed and the gastro intestinal tracts examined as outlined above. Results are shown in Table I1 as an average for all sheep in each group. Faecal egg counts were also made at this time.

Trial Il.-Eflect Against Oesophagostomum spp. The procedure outlined above was again used to test the efficiency of MK 360 against Oesophagostomum species in sheep in the New England district and the same dose rates were used. The flock of 400 had been exposed to a heavy infection ten months previously and in the sheep examined, numerous nodules were present in both the small and large intestines as well as a moderate number of mature worms.

Numbers of other species found in the control group were small and inconsistent and only figures for Oesophagosfomum are given. Results are shown in Table 111 .

Trial Ill-Eflect Aguimt Haemonchus confortus. This trial was conducted on a flock of weaners in the Carcoar district reported to be heavily infected with Haemonchus contortus. Again the same procedure and dose rates were adopted as in trials I and 11, but only abomasal contents were examined ( Table W ) .

were made that it has promising anthelmintic activity for gastro-intestinal parasites in most of the domestic animals, is highly potent with a broad anthelmintic spectrum and is well tolerated. It is further claimed that the compound is highly stable and does not stain the skin or wool.

The American workers with MK 360 using a combination of worm egg counts, elimination of worms in faeces and autopsy examinations, reached certain conclusions as to the minimum effective dose rates for sheep with the various parasites (Table 1) . However, in our trials a standard dose rate of 50 mg/Kg. b.w. was used throughout, which is somewhat lower than the American recommendation for Cooperia, Bunostomum, Nematodirus and Ostertagia species, 4 to 8 months were used. These lambs had baen weaned whbh a few days of birth and reared worm free in conpens at the Research Station.

Each of the lambs were dosed with 24,000 2 ' . colubriformis larvae and six weeks later were passing an average of 3,500 ova/g in the faeces. They were divided into 3 groups of 5, each group containing sheep with high and low faecal egg counts. After weiehinP. thoee in one group were given MK 360, and 14q9e io a second group phenothiazine. Administratiop was by rurninal injection in each case, the dose rates being as in previous trials. The five remainhg sheep were held untreated. For six day? the sheep were fed 88 before in pens and then hlled. Faeces and @stroo- intestinal organs were examined as in previous trials and results are given in Table V. Trial V-Effect on Haemonchus Oya Output. The sheep in this trial were aged M e M o s wbch hadammr+ a heavy Haemonchus infection. "lley had beep kept in pens with concrete floors at the Research Station for six months apart from a short period of when the infection was acquired. Faecal samples gave an average strongyloid egg count of 5,000 per gnun and larvae cultured from these samples were typed as 100%

Four of the sheep were weighed and dosed With.

treated. Subsequent to treatment they were held constantly in the pens, faecal samples being examined periodically for strongyloid ova. Results

In the first trial, examination of the controls showed that worms of the species Trichustrongylus (abomasal and intestinal), Ostertagiu, Nematodirus and Trichuris were present in siguificant numbers. Others present, including Hoemoffchus, Cooperiu and Chabertia spp. were insignificant and have been disregarded.

The only immature forms present were Nemutodirus spp.

The average numbers of the various species The faecal egg count (controls average-900/ gm.), showed a 100% reduction in the MK 360 group and a 97% reduction in the phenothiazine group.

In this trial only H . conlortrrh and O	ertagia spp. were present in the controls in significant numbers and other species have been disregarded. Only the aboniasa were examined and no immature forms were present.

In the MK 360 group a 96% reduction in Haemoizchus numbers was obtained with a similar result for this parasitc in the phenothiazine group. Two sheep from this latter group were missing at the time of slaughter and figures given are for eight sheep only.

Quite a marked difference in reduction of Ostertagiu spp. was seen, figures of 82% and 27% being recorded for MK 360 and phenothiazine respectively. (Table IV) .

findings in the first trial as regards the extraordinary efficiency of MK 360 against this parasite. Almost 100% reduction in worms was obtained compared with 70% in the phenothiazine group.

of M K 360 on Hnemonehw Egg Output It was not possible to daughter the 5hecp in this trial and the rcsults in Table VI records faecal cgg counts made at regular interval5 for 35 days after treatment.

In all four treated sheep ova output wac rcduced 100% by the 5th day and of these three remained Eree for the duration of the trial. The fourth sheep gave a count of 250 E.P.G on the 28th day and maintained this lcvcl approximately until the end of the trial. Output from the controls remained approximately constant throughout.

The faecal egg count (controls average 16,95O/g.) showed a 100% reduction in the MK 360 group and a 99.5% reduction in the phenothiazinc group.

Trid IV-T. cduhrifornzis As these worm free lambs had bcen artificially infected with larvae of T . coluhriformis, these were the only species of worms found at slaughter. Results arc shown in Table V and confirm the Toxicity MK 360 appears to be ncll tolerated when given orally to sheep in a dose as high as lg/Kg b.w.-twenty times the dose used in these trials.

One hundred Merino sheep of mixed ages and sexes were weighed and dosed at SO mg/Kg. These sheep had becn fed on grain and chaff for some weeks prior to treatment and none suffered ill effects. Twenty and two similar sheep were Results obtained so far evaluate this product as superior to any anthelmintic for sheep nematodes yet seen in this country, and further reports are awaited with interest.

In the small trials concluded, MK 360 has justified the claims that it is a highly efficient anthelmintic for sheep and relatively non-toxic. It is very rare for a drug to have similar activity against nematodes in different parts of the alimentary canal, but in our trials burdens of T . uxei, T . colubriformis and Oesophagostomum Summary spp. were completely removed by this chemical.

Details of three field trials and two laboratory trials giving the comparative anthelmintic effidrug, MK 3607 for sheep are described.

indicated the Of toxicity Of MK 360superior to phenothiazine against most of the important gastro-intestinal nematodes. More extensive and thorough investigations are indicated.

A great deal of work remains to be done its efficiency against immature forms. Its action against worms in other domestic animals especially cattle, pigs and poultry, should also be tested. Further trials have already begun at Glenfield chus and Oesophagostomum.

MK 360 was completely effective against all Trichostrongylus spp. in Trial I, and again with T . colubriformis in Trial IV when the drug was delivered directly into the rumen. In the stomach the H . contortus burden was reduced by g6%, with phenothiazine giving a similar figure, but MK 360 proved superior against Oytertagia with reduction figures of 97% and 82% (Trials I and III), compared with those for phenothiazine in the Same Of 75% and 27%. Reductions Of Nematodirus, both adult and immature were zine.

in the control sheep in Trial 11 were low, the 100% reduction obtained in the MK 360 group is significant. No reduction at all was recorded in Trichuris numbers, which is in contrast to results obtained in America.

The formulation supplied was very satisfactory except that difficulty was experienced in resuspending some of the solids that bad settled.

The excellent results reported in these trials were obtained without any preliminary starvation or premedication of the treated sheep, and this of toxicity, are valuable practical considerations. The lethal dose of MK 360 for sheep was not determined but it would appear to he greater than twenty times the therapeutic dose. 

fact together with the absence of any indications Drudge

The test material and most of the sheep used were provided by Messrs. Merck, Sharp and Dohme (Australia) Pty. Limited. Mr. Gordon Hendy, laboratory technician at Glenfield Veterinary Research Station carried out much of the laboratory examinations.Mr. J. C. Keast (Director of Veterinary Research, Glenfield) rendered most valuable assistance in interpretation Of results and preparing this Paper.To all the above I record my sincere appreciation.